This proposal is concerned with a study of the role that glycerol plays in the control of food intake and body weight. Since it is generally assumed that body weight is regulated through the control of body lipid content the brain must be able to monitor the amount of fat in the body. Work done in my laboratory and in others suggest that the concentration of glycerol in the blood may be one such signal. A variety of lines of research are proposed to investigate this possibility. A study currently in progress indicates that continuous infusions of very small amounts of glycerol into the cerebrospinal fluid of rats inhibit food intake in the dark but not the light phase of the diurnal cycle. This finding will be followed up by determining the minimum amount of glycerol which will inhibit food intake, and by attempting to locate regions in the central nervous system which are particularly sensitive to glycerol. This will be done by microinjection of glycerol into various hypothalamic areas and by the autoradiographic technique using radioactively labeled glycerol. The specificity of the effect of glycerol will be determined by injecting compounds which are structurally closely related to glycerol. It is also proposed to study sex differences in responsiveness to glycerol, and the reason why orally administered glycerol is ineffective, except in very large doses, in causing anorexia. Blood glycerol concentration will be measured under a variety of conditions which modify food intake and/or body weight in order to determine if food intake and body weight changes are inversely correlated with blood glycerol concentration as they should be if glycerol is in fact serving as a feedback signal. Changes in the concentration of the metabolic hormones insulin glucagon, and somatostatin will be measured in animals receiving glycerol infusions in order to determine if the concentration of these hormones reflects those of overfed or starved animals. Finally various hormones and compounds known to affect lipid metabolism and thus blood glycerol concentrations will be used in experiments designed to study their effects of food intake and body weight.